A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes.
Members of the tumour necrosis factor receptor family that contain a death domain have pleiotropic activities. They induce apoptosis via interaction with intracellular FADD/MORT1 and trigger cell growth or differentiation via TRADD and TRAF molecules. The impact of FADD/MORT1-transduced signals on T lymphocyte development was investigated in transgenic mice expressing a dominant negative mutant protein, FADD-DN. Unexpectedly, FADD-DN enhanced negative selection of self-reactive thymic lymphocytes and inhibited T cell activation by increasing apoptosis. Thus signalling through FADD/MORT1 does not lead exclusively to cell death, but under certain circumstances can promote cell survival and proliferation.
Newton
K
K
The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia.
Harris
A W
AW
Bath
M L
ML
Smith
K G
KG
Strasser
A
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002999:Clone Cells / Q000187:drug effects / Q000502:physiology; D053200:Fas-Associated Death Domain Protein; D005799:Genes, Dominant / Q000235:genetics / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D008934:Mitogens / Q000494:pharmacology; D009154:Mutation / Q000235:genetics / Q000502:physiology; D015843:Serpins / Q000235:genetics / Q000502:physiology; D018089:Superantigens / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014161:Transduction, Genetic; D019014:fas Receptor / Q000235:genetics / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505533:FADD protein, human; C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D008934:Mitogens; D015843:Serpins; D018089:Superantigens; D019014:fas Receptor